Recent studies by the principal investigator have revealed that patients with thyroid disease have a significantly higher incidence of antibodies to Yersinia enterocolitica than do controls. Studies outlined in this proposal are directed at elucidating this interesting association. Since patients with thyroid disease do not usually demonstrate symptoms of yersinosis, the presence of anti-Yersinia antibodies may reflect enhanced susceptibility to infection by this organism. This will be examined by determining whether Yersinia can be cultured in higher frequency from patients with thyroid disease than from controls. A second possible explanation for the association of anti-Yersinia antibodies with thyroid disease is that Yersinia and thyroid tissue may share common antigens. This will be assessed by, first, exposing sera with high anti-Yersinia titers to preparation of thyroid tissue to determine whether anti-Yersinia antibodies can be adsorbed. Second, animals will be immunized with thyroid tissue preparations to learn whether anti-Yersinia antibodies develop; conversely, animals will be immunized with Yersinia antigens and observed for development of antithyroid antibodies. Third, the ability of anti-Yersinia antibodies to cross-react with thyroid tissue will be examined by immunofluorescent techniques. An additional mechanism by which to explain the association of Yersinia and thyroid disease may be that Yersinia, by cross-reacting with thyroid tissue, plays a pathogenetic role through immunologic mechanism in the development of thyroid disease. The effects of immunizing animals with Yersinia on thyroid function and histology will be studied, as will the ability of immunization to induce lymphocytotoxicity to thyroid cells as assessed in an in vitro system. The studies outlined in this proposal will hopefully elucidate the relation between Yersinia and thyroid disease, increase our understanding of cross-reactions between mammalian and bacterial antigens, and provide insights into possible immunologic mechanisms responsible for certain forms of thyroid disease.